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PDBsum entry 1jqi
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Oxidoreductase
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PDB id
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1jqi
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of rat short chain acyl-Coa dehydrogenase complexed with acetoacetyl-Coa: comparison with other acyl-Coa dehydrogenases.
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Authors
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K.P.Battaile,
J.Molin-Case,
R.Paschke,
M.Wang,
D.Bennett,
J.Vockley,
J.J.Kim.
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Ref.
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J Biol Chem, 2002,
277,
12200-12207.
[DOI no: ]
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PubMed id
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Abstract
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The acyl-CoA dehydrogenases are a family of flavin adenine
dinucleotide-containing enzymes that catalyze the first step in the
beta-oxidation of fatty acids and catabolism of some amino acids. They exhibit
high sequence identity and yet are quite specific in their substrate binding.
Short chain acyl-CoA dehydrogenase has maximal activity toward butyryl-CoA and
negligible activity toward substrates longer than octanoyl-CoA. The crystal
structure of rat short chain acyl-CoA dehydrogenase complexed with the inhibitor
acetoacetyl-CoA has been determined at 2.25 A resolution. Short chain acyl-CoA
dehydrogenase is a homotetramer with a subunit mass of 43 kDa and crystallizes
in the space group P321 with a = 143.61 A and c = 77.46 A. There are two
monomers in the asymmetric unit. The overall structure of short chain acyl-CoA
dehydrogenase is very similar to those of medium chain acyl-CoA dehydrogenase,
isovaleryl-CoA dehydrogenase, and bacterial short chain acyl-CoA dehydrogenase
with a three-domain structure composed of N- and C-terminal alpha-helical
domains separated by a beta-sheet domain. Comparison to other acyl-CoA
dehydrogenases has provided additional insight into the basis of substrate
specificity and the nature of the oxidase activity in this enzyme family. Ten
reported pathogenic human mutations and two polymorphisms have been mapped onto
the structure of short chain acyl-CoA dehydrogenase. None of the mutations
directly affect the binding cavity or intersubunit interactions.
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Figure 1.
Fig. 1. The overall polypeptide folding of the SCAD
monomer. A, ribbon diagram of the SCAD monomer. Helices are
labeled A-K and  -strands
1-7. FAD is rendered in yellow and acetoacetyl-CoA in green. B,
stereo view of overlay of SCAD (blue), MCAD (red), bSCAD
(green), and IVD (gray). FAD is rendered in yellow and
acetoacetyl-CoA in indigo. Orientation of the monomer is the
same as in A. The figure was generated using Molscript (44) and
Raster3D (45).
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Figure 3.
Fig. 3. Stereo diagram of acetoacetyl-CoA and amino acid
residues involved in binding the CoA moiety in SCAD.
Acetoacetyl-CoA is rendered in ball-and-stick format, and amino
acids are rendered as sticks. The acetoacetyl-CoA is "outside"
and all amino acids are "inside" of the molecular surface of the
enzyme. The molecular surface was generated with a 1.4-Å
probe using the program Grasp (46). Molscript (44) and Raster3D
(45) were used to render the image.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
12200-12207)
copyright 2002.
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